olopatadine-hydrochloride and Rhinitis--Allergic--Perennial

To review the literature supporting current recommendations for nasal antihistamines as first-line therapy for allergic rhinitis.. Published articles in the peer-reviewed medical literature.. Clinical trials focusing on the efficacy, safety, and recommended uses of the currently approved nasal antihistamines in the United States: azelastine nasal spray, 0.1%, and olopatadine nasal spray, 0.6%.. Azelastine nasal spray, 0.1%, and olopatadine nasal spray, 0.6%, have rapid onsets of action, are well tolerated, and have clinical efficacy for treating allergic rhinitis that is equal or superior to oral second-generation antihistamines. Both also have a clinically significant effect on nasal congestion. Azelastine is also approved for nonallergic rhinitis. Although older data suggest that intranasal steroids have greater clinical efficacy than nasal antihistamines, more recent comparisons in patients with mild to moderate disease have shown equal or noninferior efficacy. In addition, in contrast to oral antihistamines or leukotriene antagonists, the combination of a nasal antihistamine and intranasal steroid may provide additive benefits for treating patients with more severe disease.. The data support current recommendations for nasal antihistamines as first-line therapy for allergic rhinitis. Future studies should address possible as needed use, the use of premixed antihistamine-steroid combinations, and the treatment of mixed rhinitis.

Topics: Administration, Intranasal; Anti-Allergic Agents; Clinical Trials as Topic; Dibenzoxepins; Humans; Olopatadine Hydrochloride; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

Olopatadine hydrochloride (CAS 140462-76-6, KW-4679, AL-4943A; hereinafter referred to as olopatadine) is a novel antiallergic drug that is a selective histamine H1 receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibits the tachykininergic contractions in guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine at doses of 0.03 mg/kg or higher reduces the symptoms of experimental allergic cutaneous responses and rhinoconjunctivitis in sensitized animals. Preclinical and clinical evaluations have demonstrated that olopatadine is a safe drug. After oral administration to healthy volunteers, olopatadine was rapidly and extensively absorbed. Unlike most other antiallergic drugs which are eliminated via hepatic metabolism, olopatadine is mainly excreted into urine. Olopatadine did not affect cytochrome P450 activities in human liver microsomes and consequently drug-drug metabolic interactions are unlikely. In double-masked clinical trials, olopatadine was shown to be effective at alleviating symptoms of allergic diseases. The drug (Allelock) was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, cutaneous pruritus, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. An ophthalmic solution of olopatadine is also useful for the treatment of allergic conjunctivitis: this formulation (Patanol) was approved in the USA and the European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively.

Topics: Animals; Anti-Allergic Agents; Conjunctivitis, Allergic; Dibenzoxepins; Histamine Antagonists; Humans; Hypersensitivity; Olopatadine Hydrochloride; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Olopatadine hydrochloride (olopatadine, 11-[(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid monohydrochloride) is a novel antiallergic/histamine H1-receptor antagonistic drug that was synthesized and evaluated in our laboratories. Oral administration of olopatadine at doses of 0.03 mg/kg or higher inhibited the symptoms of experimental allergic skin responses, rhinoconjunctivitis and bronchial asthma in sensitized guinea pigs and rats. Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig ventricular myocytes, myocardium and human ether-a-go-go-related gene channel. Olopatadine was highly and rapidly absorbed in healthy human volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was considerably low in the clearance of olopatadine in humans. Olopatadine is one of the few renal clearance drugs in antiallergic drugs. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. Ophthalmic solution of olopatadine was also approved in the United States for the treatment of seasonal allergic conjunctivitis in December, 1996 (Appendix: also in the European Union, it was approved in February 2002).

Topics: Animals; Anti-Allergic Agents; Asthma; Clinical Trials as Topic; Conjunctivitis, Allergic; Dibenzoxepins; Drug Administration Routes; Histamine H1 Antagonists; Humans; Hypersensitivity; Inflammation Mediators; Olopatadine Hydrochloride; Ophthalmic Solutions; Pruritus; Rhinitis, Allergic, Perennial; Urticaria

Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine inhibited passive cutaneous anaphylaxis in rats, experimental allergic rhinitis and bronchial asthmatic responses in actively sensitized guinea pigs. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig myocardium and ventricular myocytes. Olopatadine was highly and rapidly absorbed in healthy volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was low in the elimination of olopatadine. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000.

Topics: Animals; Anti-Allergic Agents; Clinical Trials as Topic; Depression, Chemical; Dibenzoxepins; Histamine H1 Antagonists; Humans; Inflammation Mediators; Olopatadine Hydrochloride; Passive Cutaneous Anaphylaxis; Pruritus; Rhinitis, Allergic, Perennial; Urticaria

Topics: Adolescent; Adult; Child; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic, Perennial; Time Factors; Treatment Outcome

A new formulation of olopatadine hydrochloride ophthalmic solution (olopatadine 0.2%) was evaluated in two separate, randomized, placebo-controlled, double-masked, hybrid environmental studies intended to determine efficacy and safety in subjects with histories of seasonal allergic conjunctivitis or rhinoconjunctivitis.. In these 10- and 12-week trials (conducted April-August 2003 and July-December 2001, respectively), subjects assessed their ocular signs and symptoms. Additionally, subjects in the 10-week trial evaluated the frequency of their nasal symptoms while subjects in the 12-week trial evaluated both the frequency and severity of their nasal symptoms. The two trials had a combined enrollment of 500 subjects (217 males, 283 females) including 44 children aged 10-17 years; the combined population was 81.4% Caucasian, 9.2% Black, 2% Hispanic, and 7.4% other. Daily throughout these studies, either ragweed (fall study) or grass (spring study) pollen counts were obtained from each investigative center. Slope analyses were conducted on the nasal symptom assessments by pollen count.. The nasal results from the two clinical trials are presented herein. In the fall study, relative to placebo, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0355) and itchy nose (p = 0.0032), and reduced the severity of pollen effects on sneezing (p = 0.0451), itchy nose (p = 0.0178), and runny nose (p = 0.0327). In the spring study, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0017) and runny nose (p = 0.0031) relative to placebo. In the fall trial, 2 subjects discontinued due to treatment-related adverse events (tachycardia and dry eye), while in the spring study, no subject discontinued due to a treatment-related adverse event. No subject in either study suffered a treatment-related serious adverse event.. For the subjects enrolled in these studies, olopatadine 0.2% appeared to be safe, well-tolerated, and effective in significantly reducing the frequency and/or severity of some effects of pollen on nasal symptoms.

Topics: Adolescent; Adult; Child; Conjunctivitis, Allergic; Dibenzoxepins; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Placebos; Rhinitis, Allergic, Perennial

Previous studies have suggested that olopatadine hydrochloride ophthalmic solution 0.2% administered once daily is effective for up to 24 hours after instillation and is well tolerated in adults and children aged > or =3 years.. The goal of this study was to evaluate the efficacy and safety profile of olopatadine 0.2% compared with placebo in patients with seasonal allergic conjunctivitis or rhinoconjunctivitis.. This was a 10-week, randomized, placebo-controlled, double-masked environmental study conducted during the spring allergy season (April-August) of 2003. Patients assessed their ocular signs and symptoms in terms of frequency (whole-unit scale from 0 to 5) and severity (half-unit scale from 0 to 4), and grass pollen counts were obtained daily for each investigative site. Responder analyses were conducted by pollen level (frequency based) and pollen period (severity based) to evaluate the clinical significance of differences in ocular itching and redness between treatment groups.. Two hundred sixty patients (137 females, 123 males) were enrolled in the study, including 28 children aged between 11 and 17 years; the overall population was 74% white, 11% black, 4% Hispanic, and 11% other. The frequency-based responder analyses of ocular itching and redness showed that when grass pollen counts were high (>20 gr/m(3) air), a respective 21% and 14% of patients in the olopatadine 0.2% group assessed the frequency of ocular itching and redness as >2, compared with 47% and 31% of patients in the placebo group (P < 0.001 for ocular itching; P < 0.003 for redness). The results of the severity-based responder analyses by peak pollen period were consistent with those of the frequency-based analyses. Compared with placebo, olopatadine 0.2% was associated with significant reductions in calculated mean scores for ocular itching and redness by pollen level and by pollen period. No patient was discontinued from the study because of a treatment-related adverse event, and no patient experienced a treatment-related serious adverse event.. In the patients studied, olopatadine 0.2% appeared to be effective and well tolerated when administered once daily for the treatment of the ocular signs and symptoms of allergic conjunctivitis or rhinoconjunctivitis.

Topics: Adolescent; Adult; Aged; Child; Dibenzoxepins; Double-Blind Method; Female; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Rhinitis, Allergic, Perennial; Seasons; Severity of Illness Index; Treatment Outcome

It is presumed that exposure to allergens in the environment occurs through both the eyes and the nose. Allergic rhinoconjunctivitis is typically treated with a nasal spray or systemic antihistamine, neither of which may provide adequate relief of the ocular component of the disease.. This study was designed to gain a better understanding of the physiologic interaction between the conjunctival and nasal mucosa and thus help establish a profile for the most effective ocular treatment in patients whose allergies have both an ocular and a nasal component.. This was a single-center, randomized, double-masked clinical study using the conjunctival allergen challenge (CAC) and nasal allergen challenge (NAC) models. It compared the clinical signs and symptoms induced by CAC and NAC, the effects of drugs administered by 3 different routes, and the movement of fluorescein after instillation into the eye and nose (Jones test), and assessed levels of of inflammatory mediators in tears and nasal secretions. At visit l, subjects previously identified as CAC responders underwent NAC to determine the dose of allergen necessary to elicit a sufficient positive reaction. At visit 2, which took place 1 week later, subjects with a positive reaction at visit 1 were randomized to group A (CAC) or group B (NAC), and underwent challenge to confirm the allergen dose necessary to produce a positive reaction. Subjects who qualified were randomized to receive 1 of 3 treatments: olopatadine 0.1% ophthalmic solution, placebo nasal spray, and placebo tablets; mometasone furoate monohydrate 50-microg nasal spray, placebo topical solution, and placebo tablets; or fexofenadine hydrochloride 180-mg tablets, placebo topical solution, and placebo nasal spray. All study medications were administered according to their approved labeling: drops were administered twice daily in the eyes, and the nasal sprays and tablets were administered once daily. At visit 3, which took place 1 week after visit 2, subjects received study medication and 15 minutes later underwent CAC or NAC as before. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms (sneezing, rhino rrhea/postnasal drip, nasal pruritus, palatal pruritus, and nasal congestion) rated on standard scales. Peak nasal inspiratory flow (PNIF) was measured at each visit, and the Jones test was performed at visits 1 and 3. At baseline and after challenge at visits 2 and 3, tear and nasal lavage samples were collected from a subset of randomly selected subjects for analysis of eosinophil cationic protein and tryptase.. Seventy-three subjects (42 women, 31 men; mean age, 45.26 years [range, 21-73 years]) were screened, and all were randomized to treatment. Two subjects did not complete the study. CAC induced clinically significant (>1 unit difference) ocular and nasal signs and symptoms, whereas NAC induced clinically significant nasal signs and symptoms only. In group A, there was a greater reduction in ocular itching with olopatadine compared with mometasone and fexofenadine at 3 minutes (P = 0.003 and P = 0.008, respectively) and 5 minutes (P = 0.007 and P = 0.013) after challenge. Although the difference was not statistically significant, overall relief of conjunctival redness (average of 3 vessel beds) was greatest in the olopatadine group, followed by fexofenadine. In group B, prevention of total nasal symptoms was significantly greater with mometasone compared with fexofenadine at 20 minutes (P = 0.006) and 30 minutes (P = 0.014) after challenge. There were no statistically significant differences between treatment groups in nasal symptom scores at any time point after CAC. There were also no significant differences in PNIF between treatment groups. Fluorescein was present in nasal secretions within 5 minutes of being instilled into the eye; no fluorescein was detected in the eye after instillation into the nose.. In this study, exposure of the nasal mucosa to allergen resulted in allergic rhinitis, and exposure of the ocular the ocular surface to allergen resulted in conjunctivitis with a secondary effect in the nose. These results suggest movement of allergens, their mediators, and antiallergy drugs from the ocular surfaces into the nasal cavity, with no meaningful movement from the nasal cavity to the ocular surface. In this controlled model, both the systemic agent and the nasal spray failed to control ocular symptoms. The topical ophthalmic solution provided the most effective management of allergic ocular signs and symptoms, and the nasal spray was most effective for nasal symptoms. Combined use of a nasal spray and topical ophthalmic solution may provide maximal relief in patients whose allergies have both ocular and nasal components.

Topics: Administration, Intranasal; Administration, Oral; Administration, Topical; Adult; Aged; Allergens; Anti-Allergic Agents; Conjunctiva; Conjunctivitis, Allergic; Dibenzoxepins; Double-Blind Method; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Mucosa; Olopatadine Hydrochloride; Ophthalmic Solutions; Pregnadienediols; Rhinitis, Allergic, Perennial; Tablets; Terfenadine; Time Factors

One approach to treating allergic rhinoconjunctivitis is the concomitant use of an intranasal spray such as fluticasone propionate to alleviate nasal symptoms and a topical or systemic agent to relieve ocular symptoms. It has not yet been determined whether a topical or systemic agent is more effective for the latter purpose.. This study compared the efficacy of combined use of fluticasone and olopatadine with combined use of fluticasone and fexofenadine in the treatment of the signs and symptoms of allergic rhinoconjunctivitis.. This 2-site, randomized, double-masked, placebo-controlled, parallel-group study employed the conjunctival allergen challenge (CAC) model, a standardized method of inducing ocular and nasal signs and symptoms of allergic rhinoconjunctivitis. At visit 1, subjects underwent CAC to determine the dose of allergen required to elicit a positive reaction. The allergen dose was confirmed at visit 2, and, according to a randomization schedule, subjects were dispensed fluticasone, olopatadine, and placebo pill; fluticasone, fexofenadine, and tear substitute; or placebo nasal spray, placebo pill, and tear substitute. CAC took place at visit 3, after patients had used the assigned medications for 2 weeks. Study medication was instilled 2 hours before CAC, after which allergic signs and symptoms were graded on standardized scales. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms.. Eighty subjects completed the study: 30 received fluticasone and olopatadine, 30 fluticasone and fexofenadine, and 20 placebo. Women constituted 63.8% of the study population and men 36.3%; 91.3% were white, 3.8% black, 2.5% Hispanic, 1.3% Asian, and 1.3% other. Concomitant use of fluticasone and olopatadine produced significantly greater improvements in ocular itching at 3 and 7 minutes after CAC compared with fluticasone and fexofenadine (P < 0.05). There were no significant differences in redness scores between groups; however, concomitant use of fluticasone and olopatadine produced significantly greater improvements in redness at 2 time points in each of the 3 vessel beds (ciliary, conjunctival, and episcleral) compared with placebo, and fluticasone and fexofenadine produced significantly greater improvement in redness at 1 time point in I vessel bed compared with placebo (both comparisons, P < 0.05). The 2 treatments had similar effects on total nasal symptom efficacy scores.. In this study, concomitant use of the topical agents fluticasone and olopatadine was more effective than concomitant use of fluticasone plus fexofenadine for overall treatment of the signs and symptoms of induced allergic rhinoconjunctivitis.

Topics: Administration, Intranasal; Administration, Topical; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Conjunctivitis, Allergic; Dibenzoxepins; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Histamine H1 Antagonists; Humans; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Rhinitis, Allergic, Perennial; Terfenadine; Treatment Outcome

Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Butyrophenones; Cetirizine; Child; Chlorpheniramine; Dermatitis, Atopic; Dibenzazepines; Dibenzoxepins; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Imidazoles; Japan; Male; Middle Aged; Olopatadine Hydrochloride; Pain Measurement; Piperidines; Population Surveillance; Psychomotor Performance; Pyridines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sleep Stages; Surveys and Questionnaires; Terfenadine; Urticaria

The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. In patients with AR, levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) increase. Olopatadine hydrochloride (olopatadine) is an anti-allergic agent with histamine H1 receptor antagonistic action. To investigate whether olopatadine has an effect on inflammatory reactions, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as an animal model of nasal allergy. Nasal allergy signs (sneezing, rhinorrhea and inflammation) were induced after TDI challenge. Amounts of NGF and VEGF in the nasal lavage fluid increased. Olopatadine reduced nasal allergy signs and inhibited increases in NGF and VEGF. These findings suggest that the increases in NGF and VEGF production are involved in the mechanism responsible for nasal allergy signs in TDI-challenged rats. Other histamine H1 receptor antagonists did not inhibit and instillation of histamine did not increase TDI-induced NGF and VEGF production. Therefore, olopatadine appears to exert additional biological effects other than its blockade of the histamine H(1) receptor. These results suggest that suppression of neurogenic inflammatory reactions might be partially involved in the improvement of allergy signs after treatment with olopatadine.

Topics: Animals; Anti-Allergic Agents; Dibenzoxepins; Disease Models, Animal; Histamine; Histamine H1 Antagonists, Non-Sedating; Male; Nasal Lavage Fluid; Nerve Growth Factor; Olopatadine Hydrochloride; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic, Perennial; Toluene 2,4-Diisocyanate; Vascular Endothelial Growth Factor A

CC chemokines have been shown to play an important role in inducing selective recruitment of inflammatory cells into local allergic inflammatory sites. CC chemokines are also known as histamine releasing factors. We previously showed that histamine enhances transcription of CC chemokines from nasal mucosa which leads to further induction of histamine release. This cyclic cascade may cause prolonged allergic inflammation. The aim of this study is to clarify the relationship between histamine and CC chemokine production by using human nasal epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R) antagonists in new therapeutic approaches for the treatment of nasal allergy.. HNECs were isolated from the nasal turbinates of patients diagnosed with nasal allergy. HNEC monolayers were cultured for 48 hours with or without histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L) 30 minutes before incubation with histamine. The expression of Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA.. The release of RANTES and MCP-1 was significantly upregulated by histamine compared with the control group. Both carebastine and olopatadine inhibited the release of CC chemokine production to the control level in both groups.. This study suggests that the interaction between histamine and CC chemokines may prolong allergic inflammation in human nasal mucosa. We also demonstrate the potential use of H1R antagonists in new therapeutic approaches to the treatment of nasal allergy through inhibiting this histamine-CC chemokine interaction.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Butyrophenones; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemokines, CC; Child; Dibenzoxepins; Dose-Response Relationship, Drug; Epithelial Cells; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Mucosa; Olopatadine Hydrochloride; Piperidines; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Allergen-mediated mast cell activation is a key feature of ocular allergic diseases. Evidence of eosinophil-derived mediators in tears and conjunctival biopsy specimens has been associated with chronic ocular allergic inflammation.. To examine the role of conjunctival mast cell mediators in eosinophil adhesion to conjunctival epithelial cells and eosinophil degranulation.. Conjunctival cells were obtained by enzymatic digestion of cadaveric conjunctival tissues. Eosinophils were obtained from peripheral blood samples using negative magnetic bead selection. The effect of IgE-activated mast cell supernates on eosinophil degranulation and adherence to epithelial cells was compared with supernates obtained from mast cells pretreated with a degranulation inhibitor (olopatadine). Eosinophil adhesion was measured by eosinophil peroxidase assay, and eosinophil degranulation was measured by eosinophil-derived neurotoxin radioimmunoassay.. IgE-activated conjunctival mast cell supernates stimulated adhesion of eosinophils to epithelial cells (20.4% +/- 6.3% vs 3.1% +/- 1.0%; P = .048). Degranulation was not required for this process (no effect of olopatadine). IgE-activated mast cell supernates stimulated eosinophil-derived neurotoxin release (108.89 +/- 8.27 ng/10(6) cells vs 79.45 +/- 5.21 ng/10(6) cells for controls, P = .02), which was significantly inhibited by pretreatment of mast cells with a degranulation inhibitor (79.22 +/- 4.33 ng/10(6) cells vs 61.09 +/- 5.39 ng/10(6) cells for olopatadine pretreated and untreated, respectively, P = .02).. Mediators released from conjunctival mast cells promote eosinophil adhesion to conjunctival epithelial cells and eosinophil degranulation. Degranulation inhibition studies suggest that different mast cell mediators are involved in regulation of these events.

Topics: Adolescent; Adult; Asthma; Cell Adhesion; Cell Degranulation; Conjunctiva; Dibenzoxepins; Eosinophils; Epithelial Cells; Female; Humans; Immunoglobulin E; Male; Mast Cells; Middle Aged; Olopatadine Hydrochloride; Rhinitis, Allergic, Perennial

The inhibitory effect of olopatadine, a new antiallergic drug, on antigen-induced eosinophil infiltration and its mechanisms were examined using the local sensitized rat allergic rhinitis model and isolated IL-5-stimulated rat peritoneal eosinophils. Olopatadine dose-dependently inhibited antigen-induced eosinophil infiltration in the nasal mucosa. Olopatadine dose-dependently repressed the IL-5-induced expressions of CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) on rat peritoneal eosinophils. However, olopatadine had no effect on IL-5-induced CD49d/CD29 (VLA-4) expression. These results suggest that olopatadine may inhibit antigen-induced eosinophil infiltration through repression of LFA-1 and Mac-1 expression.

Topics: Administration, Oral; Animals; Anti-Allergic Agents; Cell Movement; Dibenzoxepins; Eosinophils; Histamine H1 Antagonists; In Vitro Techniques; Integrin alpha4beta1; Lymphocyte Function-Associated Antigen-1; Macrophage-1 Antigen; Male; Nasal Mucosa; Olopatadine Hydrochloride; Phthalazines; Rats; Rhinitis, Allergic, Perennial

Effect of KW-4679, an antiallergic agent, on the experimental allergic rhinitis was studied in guinea pigs. 1) KW-4679 inhibited the sneeze response and the nasal rubbing induced after the intranasal administration of antigen in sensitized guinea pigs. The inhibitions were dose-related and significant at 0.03 mg/kg p.o. for sneeze response and 1 mg/kg p.o. for nasal rubbing, respectively. 2) The nasal vascular permeability was increased after the intranasal administration of antigen in sensitized guinea pigs. KW-4679 significantly reduced the increase of the nasal vascular permeability at 1 mg/kg p.o. or higher. From these results, KW-4679 may have inhibitory effects on sneeze, nasal irritation and rhinorrhea in clinical use.

Topics: Animals; Anti-Allergic Agents; Capillary Permeability; Dibenzoxepins; Dose-Response Relationship, Drug; Guinea Pigs; Male; Nasal Mucosa; Olopatadine Hydrochloride; Rhinitis, Allergic, Perennial